Consensus Statement on Mandatory Measurements for Pancreatic Cancer Trials for Patients With Resectable or Borderline Resectable Disease (COMM-PACT-RB): A Systematic Review and Delphi Consensus Statement.

Importance Pancreatic cancer is the third most common cause of cancer death; however, randomized clinical trials (RCTs) of survival in patients with resectable pancreatic cancer lack mandatory measures for reporting baseline and prognostic factors, which hampers comparisons between outcome measures. Objective To develop a consensus on baseline and prognostic factors to be used as mandatory measurements in RCTs of resectable and borderline resectable pancreatic cancer. Evidence Review We performed a systematic literature search of the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Embase for RCTs on resectable and borderline resectable pancreatic cancer with overall survival as the primary outcome. We produced a systematic summary of all baseline and prognostic factors identified in the RCTs. A Delphi panel that included 13 experts was surveyed to reach a consensus on mandatory and recommended baseline and prognostic factors. Findings The 42 RCTs that met inclusion criteria reported a total of 60 baseline and 19 prognostic factors. After 2 Delphi rounds, agreement was reached on 50 mandatory baseline and 20 mandatory prognostic factors for future RCTs, with a distinction between studies of neoadjuvant vs adjuvant treatment. Conclusion and Relevance This findings of this systematic review and international expert consensus have produced this Consensus Statement on Mandatory Measurements in Pancreatic Cancer Trials for Resectable and Borderline Resectable Disease (COMM-PACT-RB). The baseline and prognostic factors comprising the mandatory measures will facilitate better comparison across RCTs and eventually will enable improved clinical practice among patients with resectable and borderline resectable pancreatic cancer.

[1]  M. Boermeester,et al.  Preoperative serum ADAM12 levels as a stromal marker for overall survival and benefit of adjuvant therapy in patients with resected pancreatic and periampullary cancer. , 2021, HPB.

[2]  A. Zwinderman,et al.  Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  R. Abrams,et al.  Results of the NRG Oncology/RTOG 0848 Adjuvant Chemotherapy Question—Erlotinib+Gemcitabine for Resected Cancer of the Pancreatic Head , 2020, American journal of clinical oncology.

[4]  M. J. van de Vijver,et al.  Unsupervised class discovery in pancreatic ductal adenocarcinoma reveals cell-intrinsic mesenchymal features and high concordance between existing classification systems , 2020, Scientific Reports.

[5]  F. Motoi,et al.  Prognostic indicators in pancreatic cancer patients undergoing total pancreatectomy , 2019, Surgery Today.

[6]  M. Büchler,et al.  Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial. , 2019, JAMA surgery.

[7]  R. Van der Meer,et al.  A prognostic Bayesian network that makes personalized predictions of poor prognostic outcome post resection of pancreatic ductal adenocarcinoma , 2019, PloS one.

[8]  R. Van der Meer,et al.  A systematic review of methodological quality of model development studies predicting prognostic outcome for resectable pancreatic cancer , 2019, BMJ Open.

[9]  E. Nakakura,et al.  NCCN GUIDELINES ® INSIGHTS CE Pancreatic Adenocarcinoma , Version 1 . 2019 Featured Updates to the NCCN Guidelines , 2019 .

[10]  E. Collisson,et al.  Molecular subtypes of pancreatic cancer , 2019, Nature Reviews Gastroenterology & Hepatology.

[11]  E. Smets,et al.  Training for Medical Oncologists on Shared Decision-Making About Palliative Chemotherapy: A Randomized Controlled Trial. , 2018, The oncologist.

[12]  Thierry Lecomte,et al.  FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer , 2018, The New England journal of medicine.

[13]  R. Turkington,et al.  Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes , 2018, World journal of gastroenterology.

[14]  M. Sprangers,et al.  Prognostic and predictive factors for overall survival in metastatic oesophagogastric cancer: A systematic review and meta-analysis. , 2018, European journal of cancer.

[15]  S. Choi,et al.  Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial , 2018, Annals of surgery.

[16]  V. Torri,et al.  Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. , 2018, The lancet. Gastroenterology & hepatology.

[17]  N. Sata,et al.  Health-related quality of life of adjuvant chemotherapy with S-1 versus gemcitabine for resected pancreatic cancer: Results from a randomised phase III trial (JASPAC 01). , 2018, European journal of cancer.

[18]  R. Labianca,et al.  Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease. , 2018, The Lancet. Oncology.

[19]  M. J. van de Vijver,et al.  Clinical value of ctDNA in upper-GI cancers: A systematic review and meta-analysis. , 2017, Biochimica et biophysica acta. Reviews on cancer.

[20]  P. Catalano,et al.  An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204) , 2017, Oncology.

[21]  B. Dörken,et al.  CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  Steven J. M. Jones,et al.  Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. , 2017, Cancer cell.

[23]  Rong Lin,et al.  Analysis on survival and prognostic factors in patients with resectable pancreatic adenocarcinoma , 2017, Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban.

[24]  S. Choi,et al.  Long‐term outcomes and recurrence patterns of standard versus extended pancreatectomy for pancreatic head cancer: a multicenter prospective randomized controlled study , 2017, Journal of hepato-biliary-pancreatic sciences.

[25]  M. Büchler,et al.  Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial , 2017, The Lancet.

[26]  M. Bogdanovic,et al.  Standard versus extended lymphadenectomy in radical surgical treatment for pancreatic head carcinoma. , 2016, Journal of B.U.ON. : official journal of the Balkan Union of Oncology.

[27]  J. García-Foncillas,et al.  The Role of BRCA2 Mutation Status as Diagnostic, Predictive, and Prognosis Biomarker for Pancreatic Cancer , 2016, BioMed research international.

[28]  N. Sata,et al.  Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01) , 2016, The Lancet.

[29]  A. Vinci,et al.  Prognostic and predictive markers in pancreatic adenocarcinoma. , 2016, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[30]  R. Gibbs,et al.  Genomic analyses identify molecular subtypes of pancreatic cancer , 2016, Nature.

[31]  D. Santini,et al.  Neoadjuvant Chemoradiotherapy and Surgery Versus Surgery Alone in Resectable Pancreatic Cancer: A Single-Center Prospective, Randomized, Controlled Trial Which Failed to Achieve Accrual Targets , 2015, Journal of Gastrointestinal Surgery.

[32]  M. Shimoda,et al.  Randomized clinical trial of adjuvant chemotherapy with S‐1 versus gemcitabine after pancreatic cancer resection , 2015, The British journal of surgery.

[33]  A. Carrato,et al.  A Systematic Review of the Burden of Pancreatic Cancer in Europe: Real-World Impact on Survival, Quality of Life and Costs , 2015, Journal of Gastrointestinal Cancer.

[34]  D. Hedley,et al.  Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  W. Hohenberger,et al.  Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer , 2014, Strahlentherapie und Onkologie.

[36]  A. Bilici.  Prognostic factors related with survival in patients with pancreatic adenocarcinoma. , 2014, World journal of gastroenterology.

[37]  J. Jacob,et al.  Reduced dissemination of circulating tumor cells with no-touch isolation surgical technique in patients with pancreatic cancer. , 2014, JAMA surgery.

[38]  S. Choi,et al.  A Prospective Randomized Controlled Study Comparing Outcomes of Standard Resection and Extended Resection, Including Dissection of the Nerve Plexus and Various Lymph Nodes, in Patients With Pancreatic Head Cancer , 2014, Annals of surgery.

[39]  A. Hinke,et al.  Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. , 2013, JAMA.

[40]  C. Vollmer,et al.  Risk scores and prognostic models in surgery: pancreas resection as a paradigm. , 2012, Current problems in surgery.

[41]  D. Jäger,et al.  Open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon Alfa-2b versus fluorouracil and folinic acid for patients with resected pancreatic adenocarcinoma. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  P. Møller,et al.  The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers , 2012, British Journal of Cancer.

[43]  T. Takada,et al.  Standard versus extended lymphadenectomy in radical pancreatoduodenectomy for ductal adenocarcinoma of the head of the pancreas , 2012, Journal of hepato-biliary-pancreatic sciences.

[44]  B. Leiby,et al.  A progressive postresection walking program significantly improves fatigue and health-related quality of life in pancreas and periampullary cancer patients. , 2012, Journal of the American College of Surgeons.

[45]  Christopher G Willett,et al.  Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704--a phase III trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas. , 2012, International journal of radiation oncology, biology, physics.

[46]  M. Reni,et al.  Adjuvant PEFG (Cisplatin, Epirubicin, 5-Fluorouracil, Gemcitabine) or Gemcitabine Followed by Chemoradiation in Pancreatic Cancer: A Randomized Phase II Trial , 2012, Annals of Surgical Oncology.

[47]  R. Abrams,et al.  Fluorouracil-based Chemoradiation with Either Gemcitabine or Fluorouracil Chemotherapy after Resection of Pancreatic Adenocarcinoma: 5-Year Analysis of the U.S. Intergroup/RTOG 9704 Phase III Trial , 2011, Annals of Surgical Oncology.

[48]  L. Collette,et al.  Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[49]  H. Friess,et al.  Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. , 2010, JAMA.

[50]  H. Ueno,et al.  A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer , 2009, British Journal of Cancer.

[51]  Feng Yang,et al.  Effect of multiple‐phase regional intra‐arterial infusion chemotherapy on patients with resectable pancreatic head adenocarcinoma , 2009, Chinese medical journal.

[52]  M. Miyazaki,et al.  A randomized phase II trial of adjuvant chemotherapy with uracil/tegafur and gemcitabine versus gemcitabine alone in patients with resected pancreatic cancer , 2008, Cancer.

[53]  L. Degrate,et al.  Free-from-progression period and overall short preoperative immunotherapy with IL-2 increases the survival of pancreatic cancer patients treated with macroscopically radical surgery. , 2008, Anticancer research.

[54]  R. Abrams,et al.  Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. , 2008, JAMA.

[55]  D. Stocken,et al.  A Randomized Phase 2 Trial of Neoadjuvant Chemotherapy in Resectable Pancreatic Cancer: Gemcitabine Alone Versus Gemcitabine Combined with Cisplatin , 2007, Annals of Surgical Oncology.

[56]  Peter Neuhaus,et al.  Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. , 2007, JAMA.

[57]  E. Juozaitytė,et al.  The effect of combined treatment methods on survival and toxicity in patients with pancreatic cancer. , 2007, Medicina.

[58]  L. Seymour,et al.  Clinical Utility of Epidermal Growth Factor Receptor Expression for Selecting Patients with Advanced Non-small Cell Lung Cancer for Treatment with Erlotinib , 2006, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[59]  T. Kosuge,et al.  A multicenter randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer. , 2006, Japanese journal of clinical oncology.

[60]  D. Sargent,et al.  A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. , 2005, Surgery.

[61]  M. Imamura,et al.  Treatment of Locally Advanced Pancreatic Cancer: Should We Resect When Resectable? , 2004, Pancreas.

[62]  Helen Hickey,et al.  A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. , 2004, The New England journal of medicine.

[63]  G. Sgourakis,et al.  Regional Targeting Chemoimmunotherapy in Patients Undergoing Pancreatic Resection in an Advanced Stage of Their Disease: A Prospective Randomized Study , 2002, Annals of surgery.

[64]  I Ihse,et al.  Influence of Resection Margins on Survival for Patients With Pancreatic Cancer Treated by Adjuvant Chemoradiation and/or Chemotherapy in the ESPAC-1 Randomized Controlled Trial , 2001, Annals of surgery.

[65]  D. Kerr,et al.  Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial , 2001, The Lancet.